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Collins K.A.,The New School | Mendelsohn A.,The New School | Cain C.K.,Emotional Brain Institute | Cain C.K.,New York University | Schiller D.,The New School
Journal of Neuroscience | Year: 2014

The ability to take action in the face of threat is highly diverse across individuals. What are the neural processes that determine individual differences in the ability to cope with danger? We hypothesized that the extent of synchronization between amygdala, striatum, and medial prefrontal cortex (mPFC) would predict successful active coping performance. To test this, we developed a novel computer task based on the principals of Sidman avoidance. Healthy human participants learned through trial and error to move a marker between virtual game board compartments once every 3 s to avoid mild shocks. Behaviorally, participants exhibited large individual differences. Strikingly, both amygdala-mPFC and caudate-mPFC coupling during active coping trials covaried with final active coping performance across participants. These findings indicate that synchronization between mPFC subregions, and both amygdala and caudate predicts whether individuals will achieve successful active coping performance by the end of training. Thus, successful performance of adaptive actions in the face of threat requires functional synchronization of a neural circuit consisting of mPFC, striatum, and amygdala. Malfunction in the crosstalk between these components might underlie anxiety symptoms and impair individuals’ ability to actively cope under stress. This opens an array of possibilities for therapeutic targets for fear and anxiety disorders. © 2014 the authors. Source

Sears R.M.,New York University | Schiff H.C.,New York University | Ledoux J.E.,New York University | Ledoux J.E.,Emotional Brain Institute
Progress in Molecular Biology and Translational Science | Year: 2014

Pavlovian threat conditioning is a behavioral paradigm that has been successfully utilized to define the mechanisms underlying threat (fear) memory formation. The amygdala is a temporal lobe structure required for the acquisition, consolidation, and expression of threat (fear) memories. In particular, the lateral nucleus of the amygdala (LA) is the major input structure of the amygdala and is required for all aspects of threat learning and memory. The LA expresses many neurotransmitter and neuromodulator receptors. This chapter covers the molecular mechanisms that occur downstream of these receptors and how they influence LA-dependent Pavlovian threat learning. © 2014 Elsevier Inc. Source

Moscarello J.M.,New York University | Ledoux J.,New York University | Ledoux J.,Emotional Brain Institute
Cold Spring Harbor Symposia on Quantitative Biology | Year: 2014

Aversive Pavlovian memory coordinates the defensive behavioral response to learned threats. The amygdala is a key locus for the acquisition and storage of aversive associations. Information about conditioned and unconditioned stimuli converge in the lateral amygdala, which is a hot spot for the plasticity induced by associative learning. Central amygdala uses Pavlovian memory to coordinate the conditioned reaction to an aversive conditioned stimulus. Aversive associations can also access the brain networks of instrumental action. The offset of an aversive conditioned stimulus can reinforce behavior, recruiting a pathway that includes the lateral and basal amygdala, as opposed to the lateral and central amygdala circuit for Pavlovian reactions. Aversive conditioned stimuli can also modulate ongoing behavior, suppressing appetitive actions and facilitating aversive actions. Facilitation depends on an amygdalar network involving the lateral and central, as well as medial, nuclei. Thus, aversive Pavlovian memory has wide-reaching effects on defensive behavior, coordinating reactive to active responses to environmental threats. © 2014 Cold Spring Harbor Laboratory Press. Source

Debiec J.,New York University | Bush D.E.A.,New York University | LeDoux J.E.,New York University | LeDoux J.E.,Emotional Brain Institute
Depression and Anxiety | Year: 2011

Background: Posttraumatic stress disorder (PTSD) is associated with enhanced noradrenergic activity. Animal and human studies demonstrate that noradrenergic stimulation augments consolidation of fear learning. Retrieval of well-established memories by presenting a learned fear cue triggers reconsolidation processes during which memories may be updated, weakened, or strengthened. We previously reported that noradrenergic blockade in the rat amygdala impairs reconsolidation of fear memories. Here we investigated the effects of noradrenergic enhancement on reconsolidation of learned fear. Methods: Using auditory fear conditioning in rats, we tested the effects of postretrieval intraamygdala infusion of the β-adrenergic receptor agonist isoproterenol or the antagonist propranolol on conditioned fear in the amygdala. Results: A single intraamygdala infusion of isoproterenol following a retrieval of a well-consolidated memory enhanced fear memory elicited by the learned fear stimulus and impaired extinction of this memory 48 hr later. Intraamygdala infusion of the β-adrenergic receptor antagonist propranolol following a consecutive retrieval trial blocked the enhancing effects of isoproterenol on fear memory. Conclusions: Postretrieval β-adrenergic stimulation in the amygdala enhances reconsolidation of fear memories, making them resistant to extinction. Noradrenergic augmentation during retrieval of fear memories may thus contribute to persistence and severity of traumatic memories. Reconsolidation may be a useful tool in understanding the pathology of PTSD and may thus help in developing new and in modifying existing treatments of traumatic memories. © 2011 Wiley-Liss, Inc. Source

Courtiol E.,New York University | Courtiol E.,Emotional Brain Institute | Wilson D.A.,New York University | Wilson D.A.,Emotional Brain Institute
Journal of Neurophysiology | Year: 2014

Thalamus is a key crossroad structure involved in various functions relative to visual, auditory, gustatory, and somatosensory senses. Because of the specific organization of the olfactory pathway (i.e., no direct thalamic relay between sensory neurons and primary cortex), relatively little attention has been directed toward the thalamus in olfaction. However, an olfactory thalamus exists: the mediodorsal nucleus of the thalamus (MDT) receives input from various olfactory structures including the piriform cortex. How the MDT contributes to olfactory perception remains unanswered. The present study is a first step to gain insight into the function of the MDT in olfactory processing. Spontaneous and odor-evoked activities were recorded in both the MDT (single unit and local field potential) and the piriform cortex (local field potential) of urethane-anesthetized rats. We demonstrate that: 1) odorant presentation induces a conjoint, coherent emergence of beta-frequency-band oscillations in both the MDT and the piriform cortex; 2) 51% of MDT single units were odor-responsive with narrow-tuning characteristics across an odorant set, which included biological, monomolecular, and mixture stimuli. In fact, a majority of MDT units responded to only one odor within the set; 3) the MDT and the piriform cortex showed tightly related activities with, for example, nearly 20% of MDT firing in phase with piriform cortical beta-frequency oscillations; and 4) MDT-piriform cortex coherence was state-dependent with enhanced coupling during slowwave activity. These data are discussed in the context of the hypothesized role of MDT in olfactory perception and attention. © 2014 the American Physiological Society. Source

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